Comment on: Kim et al. (2010) Hypothalamic Angptl4/Fiaf Is a Novel Regulator of Food Intake and Body Weight. Diabetes;59:2772–2780

The article by Kim et al. (1) outlines a detailed series of experiments that purport to establish angiopoietin-like protein 4(Angptl4)/fasting- induced adipose factor (Fiaf) as a novel hypothalamic regulator of food intake and body weight in the mouse. Although the results of this study are impressive, we note that all previous publications on the regulation of fiaf in the murine brain were overlooked. For example, in our ongoing studies of adipokine gene expression in the nervous system (2), we provided the first evidence that fiaf mRNA was readily detectable, by RT-PCR and by Northern analysis, in the mouse hypothalamus, cortex, and pituitary gland (3) as well as in the rat brain following traumatic brain injury (TBI) (4). However, in contrast to the findings of Kim et al. (1), we failed to observe an effect of fasting on mouse hypothalamic fiaf mRNA (3), though the fasting-induced increase in adipose fiaf expression is in agreement with their observations. The reasons for the conflicting results in hypothalamus could be due to the use of nonidentical fasting periods, methodological discrepancy including brain dissection, and how fiaf expression was measured, or the use of different mouse strains of varying ages. Further, the evidence for FIAF immunofluorescence localized to hypothalamic neurons provided by Kim et al. (1) complements our own previously published studies where we quantified fiaf mRNA in cultured hypothalamic neurons (5,6). Moreover, we provided evidence for the CCAAT/enhancer binding protein α–dependent regulation of hypothalamic-derived fiaf (6), a transcription factor implicated in the regulation of proinflammmatory processes within the central nervous system. Additionally, fiaf gene expression was inducible in the central nervous system by lipopolysaccharide both in vitro and in vivo (7), as well as by hypoxia/ischemia (8) and TBI (4), equally suggesting a role for centrally-derived FIAF in brain injury and repair.

In conclusion, although we think that the report by Kim et al. (1) is an important contribution to the literature on brain-derived adipokines, we believe these results should have been considered in the context of previously published investigations.